Hydrochloric Acid → tert-Butyl 4-(6-(6-(4-Fluoro-3-(4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamido)phenyl)-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)-3-oxopiperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a 50-mL round-bottomed flask equipped with a magnetic stirrer and reflux condenser, 2f (240 mg, 0.570 mmol), N-(2-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide (251 mg, 0.630 mmol) and sodium carbonate (181 mg, 1.71 mmol) were mixed with DMF (16.0 mL) and water (3.0 mL). This mixture was degassed with nitrogen for 30 min. Tetrakis(triphenylphosphine)palladium (66 mg, 0.057 mmol) was added and the mixture was stirred at 100° C. (bath temperature) for 4 d. The reaction mixture was then cooled to room temperature, and water (50 mL) was added. The pH was adjusted to 6.5 with 2N hydrochloric acid and the resulting precipitate was filtered, and the filter cake was washed with ater (25 mL) and purified by column chromatography to afford a 27% yield of 2h (100 mg) as a tan foam: 1H NMR (300 MHz, DMSO-d6) δ 13.23 (s, 1H), 10.09 (s, 1H), 9.54 (s, 1H), 8.84 (s, 1H), 8.38 (4, 1H, J=2.7 Hz), 8.03 (dd, 1H, J=7.5, 2.1 Hz), 7.75 (d, 1H, J=2.7 Hz), 7.72 (s, 1H), 7.66 (m, 1H), 7.54 (d, 1H, J=9.0 Hz), 7.41 (t, 1H, 3=10.2 Hz), 4.09 (s, 2H), 3.70 (m, 4H), 2.77 (t, 2H, J=5.5 Hz), 2.62 (t, 2H, J=5.0 Hz), 1.79 (m, 4H), 1.45 (s, 9H); MS (ESI+) m/z 659.9 (M+H).

Provenance & Evidence